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Nannari Mathirai” For A STUDY ON SCIENTIFIC EVALUATION OF SIDDHA POLYHERBAL FORMULATION “NANNARI MATHIRAI” FOR HEPATOPROTECTIVE ACTIVITY ON CCL4, ETHANOL INDUCED HEPATOTOXICITY AND ANTIOXIDANT ACTIVITY IN WISTAR ALBINO RATS. The dissertation Submitted by Dr.T. MONIKA Reg. No: 321612106 Under the Guidance of Dr.M.D.SARAVANADEVI, M.D.(S)., Dissertation submitted to THE TAMILNADU DR. M.G.R MEDICAL UNIVERSITY CHENNAI-600032 In partial fulfilment of the requirements For the award of the degree of DOCTOR OF MEDICINE (SIDDHA) BRANCH-II GUNAPADAM POST GRADUATE DEPARTMENT OF GUNAPADAM THE GOVERNMENT SIDDHA MEDICAL COLLEGE CHENNAI -106 OCTOBER 2019 A STUDY ON SCIENTIFIC EVALUATION OF SIDDHA POLYHERBAL FORMULATION “NANNARI MATHIRAI” FOR HEPATOPROTECTIVE ACTIVITY ON CCL4, ETHANOL INDUCED HEPATOTOXICITY AND ANTIOXIDANT ACTIVITY IN WISTAR ALBINO RATS. The dissertation Submitted by Dr.T. MONIKA Reg. No: 321612106 Under the Guidance of Dr.M.D.SARAVANADEVI, M.D.(S)., Dissertation submitted to THE TAMILNADU DR. M.G.R MEDICAL UNIVERSITY CHENNAI-600032 In partial fulfilment of the requirements For the award of the degree of DOCTOR OF MEDICINE (SIDDHA) BRANCH-II GUNAPADAM POST GRADUATE DEPARTMENT OF GUNAPADAM THE GOVERNMENT SIDDHA MEDICAL COLLEGE CHENNAI -106 OCTOBER 2019 GOVT. SIDDHA MEDICAL COLLEGE, CHENNAI-106 DECLARATION BY THE CANDIDATE I hereby declare that this dissertation entitled A Study on Scientific Evaluation of Siddha Polyherbal formulation “NANNARI MATHIRAI” for Hepatoprotective Activity on CCL4, ETHANOL induced Hepatotoxicity and Antioxidant activity in Wistar Albino Rats is a bonafide and genuine research work carried out by me under the guidance of Dr. M.D. Saravana Devi, M.D (S), Professor, Post Graduate Department of Gunapadam, Govt.Siddha Medical College, Arumbakkam, Chennai-106 and the dissertation has not formed the basis for the award of any Degree, Diploma, Fellowship or other similar title. Date : Place : Chennai. Signature of candidate Dr.T.MONIKA GOVT. SIDDHA MEDICAL COLLEGE, CHENNAI-106 CERTIFICATE BY THE GUIDE This is to certify that the dissertation entitled A Study on Scientific Evaluation of Siddha Polyherbal formulation “NANNARI MATHIRAI” for Hepatoprotective activity on CCL4, ETHANOL induced hepatotoxicity and Antioxidant activity in Wistar Albino Rats is submitted to the Tamilnadu Dr. M. G. R. Medical University in partial fulfillment of the requirements for the award of degree of M.D (Siddha) is the bonafide and genuine research work done by Dr.T.MONIKA. Under my supervision and guidance and the dissertation has not formed the basis for the award of any Degree, Diploma, Associateship, Fellowship or other similar title. Date: Place: Seal & Signature of the Guide Dr.M.D.SARAVANADEVI.M.D(S). GOVT. SIDDHA MEDICAL COLLEGE, ARUMBAKKAM, CHENNAI-106 ENDORSEMENT BY THE HOD AND PRINCIPAL OF THE INSTITUTION This is to certify that the dissertation entitled A Study on Scientific Evaluation of Siddha Polyherbal formulation “NANNARI MATHIRAI” for Hepatoprotective activity on CCL4, ETHANOL induced hepatotoxicity and Antioxidant activity in Wistar Albino Rats is a bonafide work carried out by Dr.T.MONIKA under the guidance of Dr. M.D. Saravana Devi, M.D(S), Post Graduate Department of Gunapadam, Govt. Siddha Medical College, Chennai - 106. Date: Place: Signature of the HOD Signature of the Principal Dr.R.Meenakumari.MD(S). Dr.R.Meenakumari.MD(S). ACKNOWLEDGEMENT First and foremost, I would like to thank the Almighty for his showers and grace and the strength and caliber he gave in handling and understanding the difficulties during the tenure of this work and enabled to complete this tough task. I would like to acknowledge and extend my cordial credit to the following persons who have made the completion of this dissertation study fruitful. I hereby pledge my sincere devotion and respect to all the Siddhars who guided me eternally and dynamically. I express my sincere thanks to our Principal Prof. Dr. R. Meena kumari, M.D(S), Govt. Siddha Medical College, Chennai for her permission to perform this study and also for her valuable ideas and support throughout the course of the study. It is a genuine pleasure to express my deep sense of thanks and gratitude to my mentor and guide Dr.M.D.Saravana Devi, M.D(S), Professor, Dept of PG Gunapadam, Govt Siddha College, Chennai. Her dedication and keen interest above all his overwhelming attitude to help his students had been solely and mainly responsible for completing my work. His timely advice, meticulous scrutiny, scholarly advice and scientific approach have helped me to a very great extent to accomplish this dissertation work. I feel intensely grateful to Dr. R.Meena kumari, M.D(S), Head of Department, PG Gunapadam, Govt. Siddha Medical College, Chennai, for her valuable guidance, suggestions for completion of my whole study. I would like to express my special gratitude to Dr. R. Karolin Daisy Rani, M.D(S), Lecturer, PG Gunapadam, Govt. Siddha Medical College, Chennai, for her valuable guidance, suggestions for completion of my whole study. I owe my special thanks and sincere gratitude to my advisor Dr.V.Velpandian, M.D(S).,Ph.D., for his support towards my dissertation topic discussions and selection. His guidance helped me in all time of my research work. I express sincere thanks to our Former Principal and presently the Director General Prof. Dr. K. Kanakavalli, M.D (S)., Central Council For Research In Siddha, Ministry of AYUSH, Chennai, Govt.of India for her guidance towards this study. I wish to express my thanks to co-guide Dr. A. Ganesan, M.D(S)., Asst. Lecturer, Department of PG Gunapadam for his valuable ideas and suggestions to my study. I would like to utilize this opportunity to thank our Dept staffs Dr. K.Nalina Saraswathi, M.D(S), Dr. S. Shankar M.D(S), Dr. K.Rajamma Devi Sorubarani M.D(S) for their support and guidance. I cordially register thanks to Dr. Muralidaran, Ph.D., C.L Baid Metha College of Pharmacy, Assistant Professor advanced Centre for research for helping in the pharmacological study and advanced research for his assistance in the toxicity studies. I extended my gratitude to the animal Ethical Committee Members for their approval to do animal studies in pre-clinical studies. I wish to express my profound gratitude to Dr. R. Rajesh M.Phil, Ph.D., Director, Biogenix research center, Trivandrum, for his valuable work in Antioxidant activity. I acknowledge my thanks to Mr. Selvaraj, M.Sc, M.Phil, HOD, Department of Bio-Chemistry, Govt. Siddha Medical College, Chennai. I would like to acknowledge Dr.N.Kabilan, MD(s),Ph.D, The TamilNadu Dr.M.G.R Medical University for doing my physicochemical analysis. I express my thanks to our Librarian Mr.V.Dhandayuthapani, B.Com, M.Lib.Sc and staffs for their kind co-operation for my study. I am also thankful to Mrs. H.M.Sudha Merlin, D.Pharm, Pharmacist, Post Graduate Department of Gunapadam for her kind co-operation in purification and preparation of the trail drug for my study and successful completion of dissertation. I would like to thank Vice Chancellor, The TamilNadu Dr.M.G.R Medical University for giving permission to carry out my dissertation work and to the Additional Chief Secretary and Commissioner of Indian Medicine and Homeopathy Department, Arumbakkam, Chennai-106, for giving consent to do the dissertation. I would like my deepest thanks to my seniors for her valuable suggestions in my study. I should express my gratefulness to them for lending their helping hands whenever needed during the course of the study. Although I wish to thank extends beyond the limits of this format, I would like to thank my friends, and well-wishers for their support and inspiration throughout the dissertation work. Last but not least , I would like to pay high regards to all my family members, Father Dr.N.Thillaiarasan, Mother Mrs.T.Malarkodi, Sister T.Abinaya and My Batchmates especially Dr.R.Tamilselvan, Dr.L.Ilavarasai and V.Ponnaiya for their sincere encouragement and inspiration throughout my research work and lifting me uphill this phase of life. I owe everything to them. Besides this several people have knowingly and unknowingly helped me in the successful completion of this project. ABBREVIATIONS Alb Albumin ALP Alkaline phosphatise ALT Alanine transaminase AST Aspartate transaminase ANOVA Analysis Of Variance APAP Acetyl-Para-AminoPhenol BDL Bile Duct Ligation BHA Butylated Hydroxy Anisole BHT Butylated Hydroxy Tolune BUN Blood Urea Nitrogen CAT Catalase CCL3 Trichloromethyl CCL4 Carbon tetra chloride CD Conjugated Dienes CMC Carboxy Methyl Cellulose CPCSEA Committee for the purpose of control and supervision of experimental animals. CYP2E1 CytochromeP4502E1 DC Differential count DDT Dichloro-Diphenyl-Tricholoroethane Dep. Deposits DMN Dimethyl Nitrosamine DMSO Dimethyl sulfoxide E Eosinophil EDS Energy Dispersive X-ray Spectroscopy ABBREVIATIONS ERCP Endoscopic Retrograde Cholangiopancreatography ESR Erythrocyte Sedimentation Rate FLD Fatty Liver Disease FPC Few Pus Cells FTIR Fourier Transform Infrared Spectroscopy GIT Gastro Intestinal Tract GPx Glutathione peroxidase GSH Glutathione Hb Haemoglobin Hcl Hydrochloric acid HNO3 Nitric acid HPLC Higher Performance Liquid Chromatography HSC Hematopoietic Stem Cells IAEC Institutional Animal Ethical Committee ICMR Indian Council of Medical Research ICP-OES Inductively Coupled Plasma Optic Emission Spectroscopy L Lymphocyte MAO inhibitors Monoamine Oxidase inhibitors MDA Malondialdehyde MHI Muller Hinton Medium NASH Non Alcoholic Steato Hepatitis NAPQI N-Acetyl-P-Benzoquinoneimine NM/NNM Nannari Mathirai OECD Organisation for Economic Co-Operation & Development P Polymorphs ABBREVIATIONS PT Prothrombin Time RBC Red Blood Cell ROS Reactive Oxygen Species SEM Scanning Electron Microscope SEM Standard error mean SGOT Serum Glutamic Oxaloacetic Transaminase SGPT Serum Glutamic Pyruvic Transaminase SOD Superoxide Di Mutase TA Total Protein TAA Thioacetamide TB Total Bilirubin TBARS Thiobar Bituric Acid Reactive Substances TC Total Count TCA TetraCos15enoic acid TIBC Totaliron Binding Capacity TP Total Protein UV Ultra Violet WHO World Health Organization XRD X-Ray Diffraction studies CONTENTS S.No TITLE Page 1.
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